grazoprevir/elbasvir combination cured 93% of people with HIV and hepatitis C
co-infection, was well-tolerated and did not appear to interact with
antiretrovirals, according to final results from the C-EDGE Co-infection study
presented at the 2015 AASLD Liver Meeting last month in San Francisco.
These results confirm that people with HIV/HCV co-infection respond as well to
interferon-free therapy as those with HCV alone.
About one-third of people with HIV
worldwide are thought to be co-infected with hepatitis C virus (HCV). Over
years or decades chronic hepatitis C can progress to serious liver disease
including cirrhosis and liver cancer. People with HIV/HCV co-infection have faster
liver disease progression than those with HCV alone, on average, and liver
disease is a leading cause of death among people living with HIV. While people
living with HIV do not respond as well to interferon-based hepatitis C
treatment, there is growing evidence that this is not the case for new
direct-acting antiviral agents used in interferon-free regimens.
Jürgen Rockstroh of Bonn
University in Germany
results from the phase 3 C-EDGE Co-infection study, which tested the NS3/4
protease inhibitor grazoprevir and NS5A
inhibitor elbasvir in a fixed-dose co-formulation. Results were previously presented in part at this year's EASL
International Liver Congress and published in the August 2015 edition of The Lancet
Grazoprevir/elbasvir is undergoing US
Food and Drug Administration review with a decision expected in January 2016.
C-EDGE Co-infection included
218 previously untreated participants with HIV/HCV co-infection in Europe, the US and Australia
with HCV genotypes 1a (66%), 1b (20%), 4 (13%) or 6 (1%). More than 80% were
men, 77% were white, 17% were black and the mean age was 49 years. The median
baseline CD4 T-cell count was 568 cells/mm3 and 16% had liver
Participants could either be untreated for
HIV with a CD4 count above 500 cells/mm3 (3%) or on stable antiretroviral
therapy (ART) with more than 200 cells/mm3 and undetectable HIV RNA
(97%). Antiretrovirals permitted in this study were raltegravir (Isentress; 52%), dolutegravir (Tivicay; 27%), or rilpivirine (Edurant; 17%); 75% used tenofovir (Viread, also in Truvada) and 22% used abacavir (Ziagen,
also in Kivexa or Epzicom) as a NRTI backbone.
All participants in this open-label trial received grazoprevir/elbasvir in
a once-daily single-tablet regimen without ribavirin
for 12 weeks. The primary endpoint was sustained virological response, or
continued undetectable HCV RNA at 12 weeks after finishing treatment (SVR12).
overall SVR12 rate was 93.1% in an intention-to-treat analysis. Response rates
were similar for HCV genotypes 1a, 1b and 4 (93.1%, 93.2% and 92.9%,
respectively), and both people with genotype 6 were cured.
people – four with genotype 1a and one with
genotype 4 – relapsed after completing
treatment; four of these were on ART and one was HIV treatment-naive.
addition, two people were apparently reinfected after achieving sustained
response (both had HCV genotype 1 at baseline and genotype 3 at week 12 of
follow-up) and eight participants were lost to follow-up or discontinued
treatment for reasons unrelated to virological failure.
a modified analysis excluding the reinfections and people lost to follow-up or
non-virologic failure, the overall SVR12 rate was 97.6%, and again was similar
were no significant differences in response according to sex, age,
race/ethnicity, high or low baseline HCV RNA or cirrhosis status. All 34
participants with cirrhosis were cured, as were 96.0% of patients without
of participants had no NS5A resistance-associated variants (RAVs) at baseline
and their SVR12 rate was 98%, while 37% had NS5A RAVs and their SVR12 rate was
94% – not a significant difference.
response rates also did not differ significantly according to NRTI backbone
(97.5% with tenofovir and 95.7% with abacavir) or third antiretroviral (96.4%
with raltegravir, 100% with dolutegravir and 94.6% with rilpivirine).
with grazoprevir/elbasvir was generally safe and well-tolerated, with no drug-related
serious adverse events or discontinuations for this reason. The most common
side effects were fatigue (13%), headache (12%) and nausea (9%).
Two participants experienced transient
detectable HIV viral load during treatment but subsequently achieved undetectable
HIV RNA without changing antiretrovirals. There was no notable change in CD4
cell count from baseline to treatment week 12.
"High rates of SVR were achieved in patients
with HCV genotype 1, 4 and 6 and HIV coinfection receiving the all-oral, fixed-dose
combination of [grazoprevir/elbasvir]," the researchers concluded.
"With high SVR, low rates of adverse events, once-daily administration and
suitability for use in patients also receiving antiretroviral therapy,
[grazoprevir/elbasvir] represents another highly effective treatment option for
patients with HCV/HIV coinfection."
Rockstroh noted that the SVR12 rate in C-EDGE
Co-infection was similar to those seen in other C-EDGE trials of previously
untreated and treatment-experienced HIV-negative people, and adverse events occurred with about the same frequency, adding to
the evidence that people with HIV/HCV co-infection respond as well as HIV-negative
people and no longer need to be considered a 'special population'.
After the presentation Jay Hoofnagle of the US National
Institutes of Health said he would not necessarily assume that HCV reinfection
had taken place, since simultaneous infection with multiple genotypes can occur
and it might be that treatment eliminated genotype 1 while leaving genotype 3. Rockstroh,
however, noted that cohort studies do suggest reinfection rates of around 25%
among co-infected men who have sex with men, underlining the need for behavioural